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A novel sulfonyl chromen‐4‐ones (CHW09) preferentially kills oral cancer cells showing apoptosis, oxidative stress, and DNA damage

Author:
Tang, Jen‐Yang, Wu, Chang‐Yi, Shu, Chih‐Wen, Wang, Sheng‐Chieh, Chang, Meng‐Yang, Chang, Hsueh‐Wei
Source:
Environmental toxicology 2018 v.33 no.11 pp. 1195-1203
ISSN:
1520-4081
Subject:
DNA, DNA damage, NAD ADP-ribosyltransferase, Western blotting, acetylcysteine, antineoplastic activity, apoptosis, caspases, cell cycle, cell viability, flow cytometry, free radical scavengers, membrane potential, mitochondria, mitochondrial membrane, mouth neoplasms, neoplasm cells, oxidative stress, viability assays
Abstract:
Several functionalized chromones, the key components of naturally occurring oxygenated heterocycles, have anticancer effects but their sulfone compounds are rarely investigated. In this study, we installed a sulfonyl substituent to chromen‐4‐one skeleton and synthesized CHW09 to evaluate its antioral cancer effect in terms of cell viability, cell cycle, apoptosis, oxidative stress, and DNA damage. In cell viability assay, CHW09 preferentially kills two oral cancer cells (Ca9‐22 and CAL 27), less affecting normal oral cells (HGF‐1). Although CHW09 does not change the cell cycle distribution significantly, CHW09 induces apoptosis validated by flow cytometry for annexin V and by western blotting for cleaved poly(ADP‐ribose) polymerase (PARP), and caspases 3/8/9. These apoptosis signaling expressions are partly decreased by apoptosis inhibitor (Z‐VAD‐FMK) or free radical scavenger (N‐acetylcysteine). Furthermore, CHW09 induces oxidative stress validated by flow cytometry for the generations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), and the suppression of mitochondrial membrane potential (MMP). CHW09 also induces DNA damage validated by flow cytometry for the increases of DNA double strand break marker γH2AX and oxidative DNA damage marker 8‐oxo‐2′‐deoxyguanosine (8‐oxodG). Therefore, our newly synthesized CHW09 induces apoptosis, oxidative stress, and DNA damage, which may lead to preferential killing of oral cancer cells compared with normal oral cells.
Agid:
6165164